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FDA study of Medicare patients reaffirms safety and efficacy profile of Pradaxa® (dabigatran etexilate mesylate) for NVAF

A U.S. Food and Drug Administration (FDA) study of more than 134,000 Medicare patients found that ® (dabigatran etexilate mesylate) was associated with significantly reduced risks of , intracranial hemorrhage and death, and a significantly increased risk of major gastrointestinal hemorrhage, compared with warfarin in patients with non-valvular atrial fibrillation (NVAF).1 The study found no difference in major bleeds or myocardial infarction with PRADAXA compared to warfarin. The study, which was published online in Circulation on October 30, 2014, further reinforces the favorable benefit/risk profile of PRADAXA, as shown in the pivotal RE-LY® trial for risk reduction in NVAF.

“This is the largest and most rigorous post-marketing study of PRADAXA in routine clinical practice and supports the positive risk/benefit profile of PRADAXA,” said Sabine Luik, MD, senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “Patient safety is of utmost importance and we are pleased to see these findings further support the value of PRADAXA as a treatment option for NVAF patients.”

The FDA study is based on data from elderly patients older than 65 years enrolled in Medicare who started therapy with PRADAXA or warfarin between October 2010 and December 2012. Each group comprised 67,207 patients. The analysis showed that PRADAXA was generally associated with better patient outcomes compared to warfarin. The primary outcomes were:

  • 20 percent reduced risk of ischemic stroke (hazard ratio [HR] 0.80, 95 percent confidence interval [CI] 0.67-0.96; 205 vs. 270 events)
  • No difference in major hemorrhage (HR 0.97, CI 0.88-1.07; 777 vs. 851 events)
  • 66 percent reduced risk of intracranial hemorrhage (HR 0.34, CI 0.26-0.46; 60 vs. 186 events)
  • 28 percent increased risk of gastrointestinal bleeding (HR 1.28, CI 1.14-1.44; 623 vs. 513 events)
  • No difference in acute myocardial infarction (HR 0.92, CI 0.78-1.08; 285 vs. 327 events)

The study also found the following secondary outcomes:

  • 14 percent reduced risk of mortality (HR 0.86, CI 0.77-0.96; 603 vs. 744 events)
  • No difference in all hospitalized bleeds (HR 1.00, CI 0.92-1.09; 1079 vs. 1139 events).

The FDA had announced initial findings of their analysis in a Drug Safety Communication on its website in May 2014, stating that “As a result of our latest findings, we still consider PRADAXA to have a favorable benefit to risk profile and have made no changes to the current label or recommendations for use.” This study was performed as part of the SafeRx Project, a joint initiative of the Centers for Medicare & Medicaid Services (CMS) and the FDA.

Current Experience with PRADAXA

PRADAXA is approved to reduce the risk of stroke and systemic embolism in patients with NVAF, for the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for five to 10 days and to reduce the risk of recurrent DVT and PE in patients who have been previously treated. Nine million prescriptions for PRADAXA 150 mg and 75 mg have been filled for more than 935,000 NVAF patients in the United States since its approval in October of 2010.

PRADAXA 150 mg twice daily is the only oral anticoagulant to demonstrate superior reduction of ischemic stroke compared to warfarin in patients with NVAF. PRADAXA also demonstrated a similar rate of major bleeding events. Ischemic strokes are the most common type of stroke that NVAF patients experience.

The efficacy and safety of PRADAXA in NVAF were established in the RE-LY® trial, one of the largest stroke prevention clinical studies ever conducted with NVAF patients. The 18,113-patient RE-LY trial showed that, compared to well-controlled warfarin (N=6,022), PRADAXA 150 mg (N=6,076) significantly reduced the risk of stroke and systemic embolism by 35 percent (primary efficacy endpoint: 134 [2.2%] vs. 202 [3.4%] events, HR: 0.65, 95% CI [0.52, 0.81], P=0.0001), ischemic stroke by 25 percent (103 [1.7%] vs. 134 [2.2%] events, HR: 0.75, 95% CI [0.58, 0.97], P=0.0296) and hemorrhagic stroke by 74 percent (12 [0.2%] vs. 45 [0.8%] events, HR: 0.26, 95% CI [0.14, 0.49], P<0.0001). The rate of all-cause mortality was lower with PRADAXA 150 mg than with warfarin (3.6 percent per year versus 4.1 percent per year). PRADAXA had a higher rate of total gastrointestinal bleeds (6.1% vs. 4.0%) and major GI bleeds (1.6% vs. 1.1%; 50 percent increased risk with the 150 mg dose compared to warfarin). Treatment with PRADAXA 150 mg led to a 59 percent reduction in intracranial hemorrhage, compared to warfarin (38 vs. 90), and showed numerically lower rates of fatal and life-threatening bleeds (28 vs. 39 and 179 vs. 218, respectively).

Through the PradaxaLink™ program, patients, caregivers and health care providers can access a variety of valuable resources and 24-hour support regarding PRADAXA medication.

For an additional study on dabigatran see Dabigatran associated with higher incidence of major bleeding vs. warfarin.


Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated with Dabigatran or Warfarin for Non-Valvular Atrial Fibrillation, David J. Graham; Marsha E. Reichman; Michael Wernecke; Rongmei Zhang; Mary Ross Southworth; Mark Levenson; Ting-Chang Sheu; Katrina Mott; Margie R. Goulding; Monika Houstoun; Thomas E. MaCurdy; Chris Worrall; Jeffrey A. Kelman, Circulation, doi: 10.1161/CIRCULATIONAHA.114.012061, published online 30 October 2014.

Source: Boehringer Ingelheim Pharmaceuticals, Inc.